Mammalian gene regulation and control is being studied in a number of research projects, many of them reflecting collaborations with other laboratories. Studies on oncogenesis and differentiation. 1. A dormant oncogene has been activated in the eye lens of transgenic mice with the help of a second transgene encoding a bacterial DNA recombinase. Transgene activation in vivo will be utilized to investigate the molecular genetics of cancer initiation in the mammalian organism. 2. Oncogene mediated immortalization of primordial pituitary neurons has opened a way to understand the molecular genetics of central hypogonadism in man. 3. Analysis of human uterine cancers has revealed different mechanisms leading to the inactivation of the p53 tumor suppressor gene. Mouse models of human Gaucher disease. In an important technical feat, mutations of the glucocerebrosidase gene that cause this frequent lipid storage disorder have been introduced in the mouse germ line via homologous recombination in embryonic stem cells, and a mouse model to evaluate new avenues of therapy may be at hand soon. Chromatin structure and transgene activity have been compared in mice that express a chicken globin gene. The locus control region of this gene is sufficient to cause a chromatin configuration that mediates gene expression. The role of phosphotyrosine phosphatases in mammalian development is being addressed with the help of newly cloned mouse gene that encodes a non-receptor type enzyme. The enzyme is expressed throughout development. Functional analysis of the Zeta chain of the T-cell receptor in the mouse. Specific mutations have been introduced in the Zeta chain gene via homologous recombination in murine embryonic stem cells. After introduction in the mouse germ line, these mutations are expected to elucidate the role of the Zeta chain protein in thymocyte maturation and its requirement in the assembly and expression of the T-cell receptor.